Research Progress of Hydrogel Microneedles in Wound Management.

Microneedles are a novel drug delivery system that offers advantages such as safety, painlessness, minimally invasive administration, simplicity of use, and controllable drug delivery. As a type of polymer microneedle with a three-dimensional network structure, hydrogel microneedles (HMNs) possess excellent biocompatibility and biodegradability and encapsulate various therapeutic drugs while maintaining drug activity, thus attracting significant attention. Recently, they have been widely employed to promote wound healing and have demonstrated favorable therapeutic effects. Although there are reviews about HMNs, few of them focus on wound management. Herein, we present a comprehensive overview of the design and preparation methods of HMNs, with a particular emphasis on their application status in wound healing, including acute wound healing, infected wound healing, diabetic wound healing, and scarless wound healing. Finally, we examine the advantages and limitations of HMNs in wound management and provide suggestions for future research directions.

Nonswellable Hydrogel Patch with Tissue-Mimetic Mechanical Characteristics Remodeling In Vivo Microenvironment for Effective Adhesion Prevention.

Postoperative adhesion is a common complication after abdominal surgery, but current clinical products have unsatisfactory therapeutic effects. Here, we present a hydrogel patch formed in a single step through dialysis. The exchange of DMSO into water facilitates hydrophobic aggregate in situ formation and the formation of hydrogen bonds within the hydrogel. Thanks to the optimized component ratio and precise structural design. The hydrogel patch has soft-tissue-like mechanical characteristics, including high strength, high toughness, low modulus similar to the abdominal wall, good fatigue resistance, and fast self-recovery properties. The nonswellable hydrogel patch retains over 80% of its original mechanical properties after 7 days of immersion in physiological saline, with a maximum swelling ratio of 5.6%. Moreover, the hydrophobic biomultifunctionality of benzyl isothiocyanate can self-assemble onto the hydrogel patch during the sol-gel transition process, enabling it to remodel the inflammatory microenvironment through synergistic antibacterial, antioxidant, and anti-inflammatory effects. The hydrogel patch prevents postsurgical adhesion in a rat sidewall defect-cecum abrasion model and outperforms the leading commercial Interceed. It holds promising potential for clinical translation, considering that FDA-approved raw materials (PVA and gelatin) form the backbone of this effective hydrogel patch.

From hemostasis to proliferation: Accelerating the infected wound healing through a comprehensive repair strategy based on GA/OKGM hydrogel loaded with MXene@TiO2 nanosheets.

The treatment of infected wounds poses a formidable challenge in clinical practice due to the detrimental effects of uncontrolled bacterial infection and excessive oxidative stress, resulting in prolonged inflammation and impaired wound healing. In this study, we presented a MXene@TiO2 (MT) nanosheets loaded composite hydrogel named as GA/OKGM/MT hydrogel, which was formed based on the Schiff base reaction between adipic dihydrazide modified gelatin (GA)and Oxidized Konjac Glucomannan (OKGM), as the wound dressing. During the hemostasis phase, the GA/OKGM/MT hydrogel demonstrated effective adherence to the skin, facilitating rapid hemostasis. In the subsequent inflammation phase, the GA/OKGM/MT hydrogel effectively eradicated bacteria through MXene@TiO2-induced photothermal therapy (PTT) and eliminated excessive reactive oxygen species (ROS), thereby facilitating the transition from the inflammation phase to the proliferation phase. During the proliferation phase, the combined application of GA/OKGM/MT hydrogel with electrical stimulation (ES) promoted fibroblast proliferation and migration, leading to accelerated collagen deposition and angiogenesis at the wound site. Overall, the comprehensive repair strategy based on the GA/OKGM/MT hydrogel demonstrated both safety and reliability. It expedited the progression through the hemostasis, inflammation, and proliferation phases of wound healing, showcasing significant potential for the treatment of infected wounds.

Near Infrared-Absorbing Nanoparticle-Mediated Endovascular Photothermal Precision Embolization of Tumor Feeding Vessels for Starvation Treatment.

Photothermal therapy has attracted enormous attention as an efficient treatment modality in cancer ablation but still encounters a major bottleneck due to the limited penetration depth of light inside tissues. To overcome the challenge of deep tissue penetration, we present a strategy of endovascular photothermal precision embolization (EPPE), which employs an endovascular optical fiber to induce local embolization only in the entrance of feeding vessels through photothermal heating for the purpose of fully blocking the blood supply of the whole tumor. In EPPE, we apply a highly efficient and biocompatible photothermal agent, i.e., near-infrared (NIR)-light-absorbing diketopyrrolopyrrole-dithiophene-based nanoparticle, which exhibits a high cell-killing efficacy at a concentration of 200 µg/mL using 808 nm laser irradiation of 0.5 W/cm2 within 5 min in both 2D cell culture and a 3D tumor spheroid model. We verify the feasibility of EPPE in an ex vivo organ-structured recellularized liver model and further confirm the in vivo efficacy of the photothermal treatment in a rat liver model. The photothermal treatment combined with the embolization effect holds promise to serve as an effective starvation therapy to treat tumors of varying sizes and locations.

Nitric Oxide Scavenging and Hydrogen Sulfide Production Synergistically Treat Rheumatoid Arthritis.

To restore the disordered endogenous gas levels is an efficient alternative for the treatment of rheumatoid arthritis (RA). Both insufficient hydrogen sulfide (H2 S) and excessive nitric oxide (NO) contribute to synovial inflammation. Herein, a new block polymer PEG10 -b-PNAPA30 -b-PEG10 composed of an NO-responsive monomer and a cysteine-triggered H2 S donor, which can simultaneously scavenge NO and release therapeutic H2 S for RA treatment, is reported. In vitro experiments demonstrate that the polymer exhibits a synergistic effect on suppressing reactive oxygen species levels and pro-inflammatory cytokine production via NF-κB signaling pathway. It leads to the polarization of macrophages from M1 to M2 phenotype. Moreover, the released H2 S further restrains NO production by suppressing the expression of iNOS. In vivo experiments with an RA rat model show that the system markedly mitigates the synovial inflammation, osteoporosis, and clinical symptoms of RA rats, which is attributed to the combination therapy of H2 S release and NO depletion. This work provides new insight into the synergistic treatment of RA and endogenous gas-related diseases.

Shape-Anisotropic Microembolics Generated by Microfluidic Synthesis for Transarterial Embolization Treatment.

Particulate embolic agents with calibrated sizes, which employ interventional procedures to achieve endovascular embolization, have recently attracted tremendous interest in therapeutic embolotherapies for a wide plethora of diseases. However, the particulate shape effect, which may play a critical role in embolization performances, has been rarely investigated. Here, polyvinyl alcohol (PVA)-based shape-anisotropic microembolics are developed using a facile droplet-based microfluidic fabrication method via heat-accelerated PVA-glutaraldehyde crosslinking reaction at a mild temperature of 38 ° C. Precise geometrical controls of the microembolics are achieved with a nearly capsule shape through regulating surfactant concentration and flow rate ratio between dispersed phase and continuous phase in the microfluidics. Two specific models are employed, i.e., in vitro decellularized rabbit liver embolization model and in vivo rabbit ear embolization model, to systematically evaluate the embolization behaviors of the nonspherical microembolics. Compared to microspheres of the same volume, the elongated microembolics demonstrated advantageous endovascular navigation capability, penetration depth and embolization stability due to their comparatively smaller radial diameter and their central cylindrical part providing larger contact area with distal vessels. Such nonspherical microembolics present a promising platform to apply shape anisotropy to achieve distinctive therapeutic effects for endovascular treatments.

The evaluation of functional small intestinal submucosa for abdominal wall defect repair in a rat model: Potent effect of sequential release of VEGF and TGF-ß1 on host integration.

Ineffective vessel penetration and extracellular matrix (ECM) remodeling are responsible for the failure of porcine small intestinal submucosa (SIS)-repaired abdominal wall defects. Combined growth factors could be used as directing signals in a nature-mimicking strategy to improve this repair through mesh functionalization. In this work, vascular endothelial growth factor (VEGF) and transforming growth factor ß1 (TGF-ß1) were incorporated into a silk fibroin membrane via coaxial aqueous electrospinning to exploit their benefits of biological interactions. The membrane was sandwiched into the SIS bilayer as a functional mesh to repair partial-thickness defects in a rat model. Membrane characterization demonstrated that the core-shell structure ensured the independent distribution and sequential release of two regulators and protection of their bioactivities, which were confirmed by cell viability and protein expression. The mesh was further assessed to facilitate vasculature formation and collagen secretion in vitro, and exhibited better host integration than VEGF- or TGF-ß1-containing mesh and developed reinforced mechanical properties compared with the VEGF-containing mesh after 28 days in vivo. Determination of the underlying biological interactions revealed that rapid VEGF release promotes angiogenesis and collagen secretion but initially potentiates the inflammatory response. Sustained TGF-ß1 release at relatively low concentrations promoted VEGF for vessel permeation and maturation and steadily induced ECM remodeling under milder foreign body reactions. The functionalization of SIS improves repair by sufficient integration with timely remodeling and helps elucidate the related regulatory interactions.

Tannic acid-reinforced methacrylated chitosan/methacrylated silk fibroin hydrogels with multifunctionality for accelerating wound healing.

Natural polymeric hydrogel featuring multifunctional properties is more attractive as wound dressing. Herein, Tannic acid (TA)-reinforced methacrylated chitosan (CSMA)/methacrylated silk fibroin (SFMA) hydrogels were fabricated by two-step method of photopolymerization and TA solution incubating treatment. The TA in hydrogels not only served as second crosslinker improving the mechanical performance of up to a 5-fold increase (5 % TA treatment) than the pristine one, but also as functional molecule that endowed the hydrogels with enhanced adhesiveness and antioxidative properties. Besides, the introduction of TA into hydrogels further improved the antimicrobial activities against both Escherichia coli (E. coli) and Staphylococcus Aureus (S. aureus), as well as the cytocompatibility on fibroblasts. Moreover, it was demonstrated that the TA-treated CSMA/SFMA hydrogels could significantly promote wound healing in a full-thickness skin defect model. Collectively, these results showed that TA-reinforced CSMA/SFMA hydrogels could be a promising candidate as wound dressing.

Construction and performance evaluation of Hep/silk-PLCL composite nanofiber small-caliber artificial blood vessel graft.

To meet the growing clinical demand for small-caliber blood vessel grafts to treat cardiovascular diseases, it is necessary to develop safe and long-term unobstructed grafts. In this study, a biodegradable graft made of composite nanofibers is introduced. A composite nanofiber core-shell structure was prepared by a combination of conjugate electrospinning and freeze-dry technology. The core fiber was poly(l-lactide-co-caprolactone) (PLCL)-based and the core fibers were coated with heparin/silk gel, which acted as a shell layer. This special structure in which the core layer was made of synthetic materials and the shell layer was made of natural materials took advantage of these two different materials. The core PLCL nanofibers provided mechanical support during vascular reconstruction, and the shell heparin/silk gel layer enhanced the biocompatibility of the grafts. Moreover, the release of heparin in the early stage after transplantation could regulate the microenvironment and inhibit the proliferation of intima. All of the graft materials were biodegradable and safe biomaterials, and the degradation of the graft provided space for the growth of regenerated tissue in the late stage of transplantation. Animal experiments showed that the graft remained unobstructed for more than eight months in vivo. In addition, the regenerated vascular tissue provided a similar function to that of autogenous vascular tissue when the graft was highly degraded. Thus, the proposed method produced a graft that could maintain long-term patency in vivo and remodel vascular tissue successfully.

A biodegradable multifunctional nanofibrous membrane for periodontal tissue regeneration.

Biomaterial-based membranes represent a promising therapeutic option for periodontal diseases. Although conventional periodontal membranes function greatly in preventing the ingrowth of both fibroblasts and epithelial cells as well as connective tissues, they are not capable of promoting periodontal tissue regeneration. Here, we report a multifunctional periodontal membrane prepared by electrospinning biodegradable polymers with magnesium oxide nanoparticles (nMgO). nMgO is a light metal-based nanoparticle with high antibacterial capacity and can be fully resorbed in the body. Our results showed that incorporating nMgO into poly(L-lactic acid) (PLA)/gelatin significantly improved the overall properties of membranes, including elevated tensile strength to maintain structural stability and adjusted degradation rate to fit the time window of periodontal regeneration. Acidic degradation products of PLA were neutralized by alkaline ions from nMgO hydrolysis, ameliorating pH microenvironment beneficial for cell proliferation. In vitro studies demonstrated considerable antibacterial and osteogenic properties of nMgO-incorporated membranes that are highly valuable for periodontal regeneration. Further investigations in a rat periodontal defect model revealed that nMgO-incorporated membranes effectively guided periodontal tissue regeneration. Taken together, our data indicate that nMgO-incorporated membranes might be a promising therapeutic option for periodontal regeneration. STATEMENT OF SIGNIFICANCE: Traditional clinical treatments of periodontal diseases largely focus on the management of the pathologic processes, which cannot effectively regenerate the lost periodontal tissue. GTR, a classic method for periodontal regeneration, has shown promise in clinical practice. However, the current membranes might not fully fulfill the criteria of ideal membranes. Here, we report bioabsorbable nMgO-incorporated nanofibrous membranes prepared by electrospinning to provide an alternative for the clinical practice of GTR. The membranes not only function greatly as physical barriers but also exhibit high antibacterial and osteoinductive properties. We therefore believe that this study will inspire more practice work on the development of effective GTR membranes for periodontal regeneration.